Epidermal Growth Factor and a New Derivative

Savage, C. Richard; Cohen, Stanley

doi:10.1016/s0021-9258(19)44568-7

Cited by 1,172 publications

(46 citation statements)

References 5 publications

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“…Materials-EGF was purified from submaxillary glands as described previously (32), and EGF-Affi-Gel 10 (3.5 mg/ml gel) was prepared according to Cohen et al (33). Polyclonal rabbit 986 antibody to EGF receptor was described elsewhere (34) while anti-EGF receptor rabbit serum 2913 (specific to intracellular domain) was kindly provided by Dr. 1.…”

Section: Methodsmentioning

confidence: 99%

“…The presence of both subunit was confirmed by SOS-urea gels and Western blotting (da ta not shown ). In addition, a small amount of the -105-kOa (31 subunit (2-10% relative to (32 ) was detected in a immunoprecipitates. The other major radiolabeled proteins detected in the autoradiogram include 50-kOa and 17-kOa species corresponding, respectively, to the 1i2-and (T2-subunits of AP-2.…”

Section: Characterization Of Olc-and {3-subunit Antibodies-a Previ-mentioning

confidence: 97%

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Stoichiometric Interaction of the Epidermal Growth Factor Receptor with the Clathrin-associated Protein Complex AP-2

Sorkin

McKinsey

Shih

et al. 1995

Journal of Biological Chemistry

116

122

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Plasma membrane clathrin-associated protein complexes (AP-2) have been shown to co-immunoprecipitate with the epidermal growth factor (EGF) receptor (Sorkin A., and Carpenter, G. (1993) Science 261, 612-615). Hence, we analyzed the stoichiometry of the EGF receptor interaction with AP-2 using a new antibody that efficiently immunoprecipitates native AP-2. EGF receptor AP-2 complexes were isolated from 35S-labeled cells treated with EGF by EGF receptor affinity chromatography followed by precipitation with the antibody to AP-2. Quantitation of the relative molar concentrations of the proteins found in the complex revealed that 1 mol of AP-2 was associated with approximately 1.1 mol of EGF receptor. No other proteins were present in significant molar concentrations relative to AP-2, indicating that other proteins are not stoichiometrically involved in the interaction of EGF receptors and AP-2 in vivo. Co-immunoprecipitation experiments in cells expressing a mutant EGF receptor demonstrated that the cytoplasmic carboxyl-terminal 214 residues of the EGF receptor are essential for interaction with AP-2.

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Section: Methodsmentioning

confidence: 99%

Section: Characterization Of Olc-and {3-subunit Antibodies-a Previ-mentioning

confidence: 97%

Stoichiometric Interaction of the Epidermal Growth Factor Receptor with the Clathrin-associated Protein Complex AP-2

Sorkin

McKinsey

Shih

et al. 1995

Journal of Biological Chemistry

116

122

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“…Materials. EGF was purified from mouse salivary glands as described previously (58). Human sequence angiotensin II (Asp Arg Val Tyr Ile His Pro Phe), [Arg8]vasopressin, (-)-epinephrine (Sigma), and EGF were prepared as 100fold-concentrated solutions in 10 mM NaPi-150 mM NaCl (pH 7.4) containing 0.1% bovine serum albumin.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II Stimulates Protein-Tyrosine Phosphorylation in a Calcium-Dependent Manner

Huckle

Prokop

et al. 1990

Molecular and Cellular Biology

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Cellular responses to epidermal growth factor (EGF) are dependent on the tyrosine-specific protein kinase activity of the cell-surface EGF receptor. Previous studies using WB rat liver epithelial cells have detected at least 10 proteins whose phosphotyrosine (P-Tyr) content is increased by EGF. In this study, we have examined alternate modes of activating tyrosine phosphorylation. Treatment of WB cells with hormones linked to Ca2+ mobilization and protein kinase C (PKC) activation, including angiotensin II, [Arg8]vasopressin, or epinephrine, stimulated rapid (less than or equal to 15-s) and transient increases in the P-Tyr content of several proteins (p120/125, p75/78, and p66). These proteins, detected by anti-P-Tyr immunoblotting, were similar in molecular weight to a subset of EGF-sensitive P-Tyr-containing proteins (P-Tyr-proteins). The increased P-Tyr content was confirmed by [32P]phosphoamino acid analysis of proteins recovered by anti-P-Tyr immunoprecipitation. Elevating intracellular [Ca2+] with the ionophore A23187 or ionomycin or with the tumor promoter thapsigargin mimicked the effects of hormones on tyrosine phosphorylation, whereas treatment with a PKC-activating phorbol ester did not. In addition, responses to angiotensin II were not diminished in PKC-depleted cells. Ca2+ mobilization, measured by fura-2 fluorescence, was coincident with the increase in tyrosine phosphorylation in response to angiotensin II or thapsigargin. Loading cells with the intracellular Ca2+ chelator bis-(o-aminophenoxy)ethane-N ,N ,N' , N'-tetraacetic acid (BAPTA) inhibited the appearance of all P-Tyr-proteins in response to angiotensin II, thapsigargin, or ionophores, as well as two EGF-stimulated P-Tyr-proteins. The majority of EGF-stimulated P-Tyr-proteins were not affected by BAPTA. These studies indicate that angiotensin II can alter protein-tyrosine phosphorylation in a manner that is secondary to, and apparently dependent on, Ca2+ mobilization. Thus, ligands such as EGF and angiotensin II, which act through distinct types of receptors, may activate secondary pathways involving tyrosine phosphorylation. These results also raise the possibility that certain growth-promoting effects of Ca2+ -mobilizing agents such as angiotensin II may be mediated via tyrosine phosphorylation.

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“…Studying the nerve cells at more frequent intervals, she noted that these cells did proliferate initially, but then died because the limb bud was not producing the putative growth factors needed for their survival. NGF was later isolated by Stanley Cohen, a biochemist who joined Levi-Montalcini and later shared the Nobel Prize with her, not before identifying both the second growth factor, the epidermal growth factor (EGF) [1] and the respective cell surface receptor (EGFR) [2]. Michael Waterfield and colleagues made the first link to cancer.…”

Section: Introductionmentioning

confidence: 99%

EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance

Uribe

Marrocco

Yarden

2021

Cancers

216

145

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The epidermal growth factor receptor (EGFR) has served as the founding member of the large family of growth factor receptors harboring intrinsic tyrosine kinase function. High abundance of EGFR and large internal deletions are frequently observed in brain tumors, whereas point mutations and small insertions within the kinase domain are common in lung cancer. For these reasons EGFR and its preferred heterodimer partner, HER2/ERBB2, became popular targets of anti-cancer therapies. Nevertheless, EGFR research keeps revealing unexpected observations, which are reviewed herein. Once activated by a ligand, EGFR initiates a time-dependent series of molecular switches comprising downregulation of a large cohort of microRNAs, up-regulation of newly synthesized mRNAs, and covalent protein modifications, collectively controlling phenotype-determining genes. In addition to microRNAs, long non-coding RNAs and circular RNAs play critical roles in EGFR signaling. Along with driver mutations, EGFR drives metastasis in many ways. Paracrine loops comprising tumor and stromal cells enable EGFR to fuel invasion across tissue barriers, survival of clusters of circulating tumor cells, as well as colonization of distant organs. We conclude by listing all clinically approved anti-cancer drugs targeting either EGFR or HER2. Because emergence of drug resistance is nearly inevitable, we discuss the major evasion mechanisms.

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Epidermal Growth Factor and a New Derivative

Cited by 1,172 publications

References 5 publications

Stoichiometric Interaction of the Epidermal Growth Factor Receptor with the Clathrin-associated Protein Complex AP-2

Stoichiometric Interaction of the Epidermal Growth Factor Receptor with the Clathrin-associated Protein Complex AP-2

Angiotensin II Stimulates Protein-Tyrosine Phosphorylation in a Calcium-Dependent Manner

EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance

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